Skip to main content

Advertisement

SpringerLink
Log in

High prevalence of specific KIR types in patients with HHV-8 positive cutaneous vascular lesions: a possible predisposing factor?

  • Concise Communication
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Human herpesvirus 8 (HHV8) has been hypothesized to be a potential cofactor for the development of diverse cutaneous vascular proliferative lesions, including eruptive cherry angiomas. Recent reports evidenced the influence of killer cell immunoglobulin-like receptor (KIR) gene diversity in defining the susceptibility to symptomatic herpesvirus infections. In this study, skin samples from vascular lesions and healthy controls were characterized simultaneously for the presence of HHV8 and for the KIR genotype, focusing upon the presence of the KIR2DL2/DS2 and KIR2DL3 genes, which have been associated to herpesvirus susceptibility. The results showed that about 64 % of the vascular lesions resulted positive for the presence of HHV8, whereas no control healthy skin samples harbored HHV8 DNA. HHV8-positive patients had a significantly increased frequency of KIR2DL2/DS2 homozigosity and a concomitant decrease of the homozygous KIR2DL3 genotype, compared to healthy controls or HHV8-negative patients. Notably, the simultaneous presence of KIR2DL2/DS2 homozygosity and HHV8 infection resulted in a significantly increased risk to develop cutaneous lesions (OR 5.7) compared to the individual factors alone, suggesting that specific KIR genotypes might predispose to HHV8 symptomatic infection, allowing the virus to exert its angioproliferative activity at skin level.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Borghi A, Benedetti S, Corazza M, Gentili V, Ruina G, Di Luca D, Virgili A, Caselli E (2013) Detection of human herpesvirus 8 sequences in cutaneous cherry angiomas. Arch Dermatol Res 305:659–664

    Article  PubMed  Google Scholar 

  2. Borghi A, Caselli E, Di Luca D, Sebastiani A, Perri P, Seraceni S, Contini C, Virgili A (2013) Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report. Infect Agent Cancer 8:41

    Article  PubMed  PubMed Central  Google Scholar 

  3. Brown EE, Whitby D, Vitale F, Fei PC, Del Carpio C, Marshall V, Alberg AJ, Serraino D, Messina A, Gafa L, Goedert JJ (2005) Correlates of human herpesvirus-8 DNA detection among adults in Italy without Kaposi sarcoma. Int J Epidemiol 34:1110–1117

    Article  PubMed  Google Scholar 

  4. Caselli E, Benedetti S, Grigolato J, Caruso A, Di Luca D (2012) Activating transcription factor 4 (ATF4) is upregulated by human herpesvirus 8 infection, increases virus replication and promotes proangiogenic properties. Arch Virol 157:63–74

    Article  CAS  PubMed  Google Scholar 

  5. Caselli E, Fiorentini S, Amici C, Di Luca D, Caruso A, Santoro MG (2007) Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1-dependent capillary-like structure formation: role of the IKK/NF-{kappa}B pathway. Blood 109:2718–2726

    CAS  PubMed  Google Scholar 

  6. Caselli E, Rizzo R, Ingianni A, Contini P, Pompei R, Di Luca D (2014) High prevalence of HHV8 infection and specific killer cell immunoglobulin-like receptors allotypes in Sardinian patients with type 2 diabetes mellitus. J Med Virol 86:1745–1751

    Article  CAS  PubMed  Google Scholar 

  7. Cattani P, Cerimele F, Porta D, Graffeo R, Ranno S, Marchetti S, Ricci R, Capodicasa N, Fuga L, Amico R, Cherchi G, Gazzilli M, Zanetti S, Fadda G (2003) Age-specific seroprevalence of human herpesvirus 8 in Mediterranean regions. Clin Microbiol Infect 9:274–279

    Article  CAS  PubMed  Google Scholar 

  8. Cerwenka A, Lanier LL (2001) Natural killer cells, viruses and cancer. Nat Rev Immunol 1:41–49

    Article  CAS  PubMed  Google Scholar 

  9. Cook M, Briggs D, Craddock C, Mahendra P, Milligan D, Fegan C, Darbyshire P, Lawson S, Boxall E, Moss P (2006) Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation. Blood 107:1230–1232

    Article  CAS  PubMed  Google Scholar 

  10. Di Bona D, Scafidi V, Plaia A, Colomba C, Nuzzo D, Occhino C, Tuttolomondo A, Giammanco G, De Grazia S, Montalto G, Duro G, Cippitelli M, Caruso C (2014) HLA and killer cell immunoglobulin-like receptors influence the natural course of CMV infection. J Infect Dis 210:1083–1089

    Article  PubMed  Google Scholar 

  11. Estefania E, Gomez-Lozano N, Portero F, de Pablo R, Solis R, Sepulveda S, Vaquero M, Gonzalez MA, Suarez E, Roustan G, Vilches C (2007) Influence of KIR gene diversity on the course of HSV-1 infection: resistance to the disease is associated with the absence of KIR2DL2 and KIR2DS2. Tissue Antigens 70:34–41

    Article  CAS  PubMed  Google Scholar 

  12. Jham BC, Ma T, Hu J, Chaisuparat R, Friedman ER, Pandolfi PP, Schneider A, Sodhi A, Montaner S (2011) Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi’s sarcoma. PLoS One 6:e19103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jones DC, Peacock S, Hughes D, Traherne JA, Allen RL, Barnardo MC, Friend P, Taylor CJ, Fuggle S, Trowsdale J, Young NT (2014) Killer immunoglobulin-like receptor gene repertoire influences viral load of primary human cytomegalovirus infection in renal transplant patients. Genes Immunol 15:562–568

    Article  CAS  Google Scholar 

  14. Kaplan LD (2013) Human herpesvirus-8: Kaposi sarcoma, multicentric Castleman disease, and primary effusion lymphoma. Hematology Am Soc Hematol Educ Program 2013:103–108

    PubMed  Google Scholar 

  15. Lanier LL (1998) NK cell receptors. Annu Rev Immunol 16:359–393

    Article  CAS  PubMed  Google Scholar 

  16. Ma T, Jham BC, Hu J, Friedman ER, Basile JR, Molinolo A, Sodhi A, Montaner S (2010) Viral G protein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi’s sarcoma. Proc Natl Acad Sci USA 107:14363–14368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Moesta AK, Norman PJ, Yawata M, Yawata N, Gleimer M, Parham P (2008) Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3. J Immunol 180:3969–3979

    Article  CAS  PubMed  Google Scholar 

  18. Montaner S, Sodhi A, Molinolo A, Bugge TH, Sawai ET, He Y, Li Y, Ray PE, Gutkind JS (2003) Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi’s sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell 3:23–36

    Article  CAS  PubMed  Google Scholar 

  19. Moraru M, Cisneros E, Gomez-Lozano N, de Pablo R, Portero F, Canizares M, Vaquero M, Roustan G, Millan I, Lopez-Botet M, Vilches C (2012) Host genetic factors in susceptibility to herpes simplex type 1 virus infection: contribution of polymorphic genes at the interface of innate and adaptive immunity. J Immunol 188:4412–4420

    Article  CAS  PubMed  Google Scholar 

  20. Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223

    Article  CAS  PubMed  Google Scholar 

  21. Morris VA, Punjabi AS, Wells RC, Wittkopp CJ, Vart R, Lagunoff M (2012) The KSHV viral IL-6 homolog is sufficient to induce blood to lymphatic endothelial cell differentiation. Virology 428:112–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Naranatt PP, Krishnan HH, Svojanovsky SR, Bloomer C, Mathur S, Chandran B (2004) Host gene induction and transcriptional reprogramming in Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8)-infected endothelial, fibroblast, and B cells: insights into modulation events early during infection. Cancer Res 64:72–84

    Article  CAS  PubMed  Google Scholar 

  23. Rizzo R, Gentili V, Casetta I, Caselli E, De Gennaro R, Granieri E, Cassai E, Di Luca D, Rotola A (2012) Altered natural killer cells’ response to herpes virus infection in multiple sclerosis involves KIR2DL2 expression. J Neuroimmunol 251:55–64

    Article  CAS  PubMed  Google Scholar 

  24. Schulz TF, Cesarman E (2015) Kaposi Sarcoma-associated Herpesvirus: mechanisms of oncogenesis. Curr Opin Virol 14:116–128

    Article  CAS  PubMed  Google Scholar 

  25. Tanzi E, Zappa A, Caramaschi F, Amendola A, Lasagna D, Gatti L, Ascoli V, Rezza G, Zanetti AR (2005) Human herpesvirus type 8 infection in an area of Northern Italy with high incidence of classical Kaposi’s sarcoma. J Med Virol 76:571–575

    Article  PubMed  Google Scholar 

  26. Winter CC, Gumperz JE, Parham P, Long EO, Wagtmann N (1998) Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition. J Immunol 161:571–577

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was financially supported by local University research funds (FAR 2013, University of Ferrara).

Author information

Authors and Affiliations

  1. Section of Dermatology and Infectious Diseases, Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Alessandro Borghi, Annarosa Virgili & Monica Corazza

  2. Section of Microbiology and Medical Genetics, Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Maria D’Accolti, Roberta Rizzo, Dario Di Luca & Elisabetta Caselli

Authors
  1. Alessandro Borghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria D’Accolti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberta Rizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Annarosa Virgili
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dario Di Luca
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Monica Corazza
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elisabetta Caselli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elisabetta Caselli.

Ethics declarations

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Borghi, A., D’Accolti, M., Rizzo, R. et al. High prevalence of specific KIR types in patients with HHV-8 positive cutaneous vascular lesions: a possible predisposing factor?. Arch Dermatol Res 308, 373–377 (2016). https://doi.org/10.1007/s00403-016-1643-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-016-1643-x

Keywords

Search

Navigation